Antibody-Drug Conjugate Offers Modest Improvement in Ovarian Cancer

An antibody-drug conjugate known as lifastuzumab vedotin offered a numerical but not statistically significant improvement in progression-free survival (PFS) over pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer, according to a new phase II study.

“Single agents approved for platinum-resistant ovarian cancer have overall response rates from 6.5% to 20.5% and a PFS from 2 to 6 months. Thus, there is an urgent need for more effective therapies,” wrote study authors led by Joyce F. Liu, MD, MPH, of the Dana-Farber Cancer Institute in Boston.

Lifastuzumab vedotin (LIFA) is a conjugate of a humanized immunoglobulin G1 anti-NaPi2b monoclonal antibody and the antimitotic agent monomethyl auristatin E. NaPi2b is expressed in ovarian cancer, as well as other malignancies including non–small-cell lung cancer and papillary thyroid cancer; a phase I trial showed that LIFA was well tolerated with potential antitumor activity in platinum-resistant ovarian cancer patients.

The new phase II study included 95 patients randomized to either LIFA given intravenously every 3 weeks (47 patients) or to standard care with pegylated liposomal doxorubicin (PLD); 93 patients received at least one dose of the study drug. Patients were followed for a median of 6.6 months; the results were published in Annals of Oncology.

The median PFS with LIFA was 5.3 months, compared with 3.1 months for PLD, for a hazard ratio (HR) of 0.78 (95% CI, 0.46–1.31; P = .34). In patients with high expression of NaPi2b, the rates were similar, with a median PFS with LIFA of 5.3 months and 3.4 months with PLD, for an HR of 0.71 (95% CI, 0.40–1.26; P = .24).

In the full cohort, the objective response rate to the therapy was 34% with LIFA and 15% with PLD (P = .03). In the NaPi2b-high group, those rates were 36% and 14%, respectively (P = .02). The median duration of response was 5.5 months with LIFA and 3.9 months with PLD in the full cohort.

“This study was hypothesis generating and was designed to detect only a large benefit of LIFA monotherapy,” the authors wrote, adding that the study confirms that antibody-drug conjugates can have significant clinical activity in platinum-resistant ovarian cancer. “However, this study also highlights that objective response rate alone may not translate to durable responses with [antibody-drug conjugates], and that careful target selection, evaluation of target expression thresholds, response rate, and duration of response may all be important to the future development of antibody-directed cytotoxics in ovarian cancer.”